Coverage Policy Manual - Arkansas Blue Cross and Blue Shield

Coverage Policy Manual
Policy #:	2006005
Category:	Radiology
Initiated:	February 2006
Last Review:	August 2023

Carotid Intima -Media Thickness, Ultrasound Measurement to Assess Subclinical Atherosclerosis

Description:

Ultrasonographic measurement of carotid intima-medial (or intimal-media) thickness (CIMT) refers to the use of B-mode ultrasound to determine the thickness of the two innermost layers of the carotid artery wall, the intima and the media. Detection and monitoring of intima-medial thickening, which is a surrogate marker for atherosclerosis, may provide an opportunity to intervene earlier in atherogenic disease and/or monitor disease progression.

Heart disease is the leading cause of mortality in the United States, accounting for more than half of all deaths. Coronary heart disease (CHD), also known as coronary artery disease, is the most common cause of heart disease (Tsao, 2023). In a 2023 update on heart disease and stroke statistics from the American Heart Association, it was estimated that 720,000 Americans have a new coronary attack (first hospitalized myocardial infarction or CHD death) and 335,000 have a recurrent attack annually. An estimated 20.5 million Americans ≥20 years of age have CHD. The prevalence of CHD was higher for males than females in all age groups. Total CHD prevalence is 7.1% in US adults ≥20 years of age; CHD prevalence is 8.7% for males and 5.8% for females. On the basis of data from the 2018 National Health Interview Survey, CHD prevalence estimates are 5.7% among White people, 5.4% among Black people, 8.6% among American Indian/Alaska Native people, and 4.4% among Asian people ≥18 years of age.

Established major risk factors for CHD have been identified by the National Cholesterol Education Program Expert Panel (NCEP). These risk factors include elevated serum levels of low-density lipoprotein (LDL) cholesterol and total cholesterol, and reduced levels of high-density lipoprotein (HDL) cholesterol. Other risk factors include a history of cigarette smoking, hypertension, family history of premature CHD, and age.

The third report of the National Cholesterol Education Program (NCEP) Adult Treatment Panel established various treatment strategies to modify the risk of CHD, with emphasis on target goals of LDL. Pathology studies have demonstrated that levels of traditional risk factors are associated with the extent and severity of atherosclerosis. The third report of the National Cholesterol Education Program Adult Treatment Panel recommended use of the Framingham criteria to further stratify those patients with 2 or more risk factors for more intensive lipid management (Pasternak, 2003). However, at every level of risk factor exposure, there is substantial variation in the amount of atherosclerosis, presumably related to genetic susceptibility and the influence of other risk factors. Therefore, there has been interest in identifying a technique that can improve the ability to diagnose those at risk of developing CHD, as well as measure disease progression, particularly for those at intermediate risk.

The carotid arteries can be well-visualized by ultrasonography, and ultrasonographic measurement of the carotid intima-medial thickness (CIMT) has been investigated as a technique to identify and monitor subclinical atherosclerosis. B-mode ultrasound is most commonly used to measure CIMT. The intima-medial thickness (IMT) is measured and averaged over several sites in each carotid artery. Imaging of the far wall of each common carotid artery yields more accurate and reproducible IMT measurements than imaging of the near wall. Two echogenic lines are produced, representing the lumen-intima interface and the media-adventitia interface. The distance between these 2 lines constitutes the IMT.

Regulatory Status

In 2003, SonoCalc® (SonoSite) was cleared for marketing by the U.S. Food and Drug Administration (FDA) through the 510(k) process. The FDA determined that this software was substantially equivalent to existing image display products for use in the automatic measurement of the IMT of the carotid artery from images obtained from ultrasound systems. Subsequently, several other devices have been approved through the 510(k) process.

FDA product code: LLZ.

Policy/
Coverage:

Effective August 2021

Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria

Ultrasonographic measurement of carotid artery intimal-medial thickness (IMT) as a technique of identifying and monitoring subclinical atherosclerosis does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness.

For members with contracts without primary coverage criteria, ultrasonographic measurement of carotid artery intimal-medial thickness (IMT) as a technique of identifying and monitoring subclinical atherosclerosis is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.

Effective Prior to August 2021

Ultrasonographic measurement of carotid artery intimal-medial thickness (IMT) as a technique of identifying and monitoring subclinical atherosclerosis is not covered based on benefit certificate primary coverage criteria that there be scientific evidence of effectiveness.

For contracts without primary coverage criteria, ultrasonographic measurement of carotid artery intimal-medial thickness (IMT) as a technique of identifying and monitoring subclinical atherosclerosis is considered investigational and is not covered. Investigational services are an exclusion in the member benefit contract.

Rationale:

There are multiple observational studies correlating measurements of carotid IMT with either established risk factors for CHD or the incidence of cardiovascular events. For example, in the Atherosclerosis Risk in Communities (ARIC) study, the authors evaluated risk factors associated with increased carotid IMT in 15,800 subjects. Carotid IMT had a graded relationship with increasing quartiles of plasma total cholesterol, LDL cholesterol, and triglycerides. Carotid IMT was then also correlated with the incidence of coronary heart disease in a subgroup of patients enrolled in the trial after 4 to 7 years of follow-up. Among the 12,841 subjects studied, there were 290 incident events. The hazard ratio rate for men and women, adjusted for age and sex, comparing extreme carotid IMT (i.e., >/= 0.1mm) to non-extreme IMT (i.e., < 0.1mm) was 5.07 for women and 1.85 for men. The strength of the relationship was reduced by including major CHD risk factors, but remained elevated for higher measurements of carotid IMT. The authors concluded that mean carotid IMT is a noninvasive predictor of future CHD incidence.

The Rotterdam Study was a prospective cohort study that started in 1989 and recruited 7,983 men and women aged 55 years and over. The main objective of the Rotterdam Study was to investigate the prevalence and incidence of risk factors for chronic diseases in the elderly, including cardiovascular disease. One aspect of the study sought to determine whether progression of atherosclerosis in asymptomatic elderly subjects is a prelude to cardiovascular events. Measurements of carotid IMT were used to assess the progression of atherosclerosis. Increasing carotid IMT was associated with increasing risks of stroke and MI. O'Leary and colleagues performed carotid IMT in 4,476 asymptomatic subjects aged 65 years or older without clinical cardiovascular disease. The incidence of cardiovascular events correlated with measurements of carotid IMT thickness; this association remained significant after adjustment for traditional risk factors. The authors conclude that increases in the thickness of carotid IMT are directly associated with an increased risk of myocardial infarction and stroke in older adults without a history of cardiovascular disease. Hodis and colleagues studied 146 men aged 40 to 59 years old who previously had coronary artery bypass surgery. Subjects underwent measurements of carotid IMT every 6 months and underwent coronary angiography at baseline and every 2 years. Average follow-up was 8.8 years. For each 0.03-mm increase in carotid IMT, the relative risk for nonfatal myocardial infarction or coronary death was 2.2, and the relative risk for any coronary event was 3.1. Absolute thickness and progression in thickness predicted risk for coronary events beyond that predicted by coronary arterial measures of atherosclerosis and lipid measurements. The authors reported that ultrasonographic monitoring carotid IMT may be a useful surrogate endpoint for clinical coronary events.

Several other studies have, in fact, used carotid IMT measurements as outcome measures. In this setting, serial measurements of carotid IMT are performed as opposed to a single measure. For example, the Asymptomatic Carotid Artery Progression Study (ACAPS) was designed to evaluate the role of lovastatin (a HMG-CoA reductase inhibitor, i.e., a statin drug) in patients asymptomatic for cardiovascular disease and with LDL cholesterol levels at or below the limits established by the National Cholesterol Education Program. A total of 919 asymptomatic men and women were randomized to receive various combinations of lovastatin, warfarin, and placebo over a 3-year period. The principal outcome measurement was the progression of carotid IMT, tested at 6 sites in both carotid arteries. Lovastatin treatment was associated with a reduction in the progression of mean maximum carotid IMT. The Monitored Atherosclerosis Regression Study also included measurements of carotid IMT every 6 months for 4 years in a subset of enrolled subjects. The authors concluded that lipid-lowering therapy resulted in a regression of carotid IMT.

It is evident from a literature search that ultrasonographic measurement of carotid IMT has emerged as a research tool for the assessment of subclinical atherosclerosis, which has been incorporated into clinical trials as an outcome measure. However, it is unclear how this measurement can be used to benefit patient management. One proposal is to use carotid IMT as an additional risk factor to further categorize those patients who would be classified as at an "intermediate risk" for CHD on the basis of established CHD risk factors, such as total cholesterol, LDL cholesterol, and HDL cholesterol levels. Identification of additional independent risk factors might then be able to identify those intermediate risk patients who might benefit from more aggressive risk reduction. As noted in the Discussion section, there is substantial variation in the extent and severity of atherosclerosis among patients considered to be at similar risk based on traditional risk factors. Therefore, measurements of carotid IMT could be used to provide incremental information to traditional risk factor assessment. In the National Cholesterol Expert Panel (NCEP) Adult Treatment Panel III (ATP III) report, carotid intimal thickness was identified as an "emerging non-lipid risk factor” and offered the following comments:

"One test in this category [tests for atherosclerotic plaque burden] is carotid sonography used to measure intimal medial thickness (IMT) of the carotid arteries. The extent of carotid atherosclerosis correlates positively with the severity of coronary atherosclerosis. Furthermore, recent studies show that severity of IMT independently correlates with risk for major coronary events. Thus, measurement of carotid IMT theoretically could be used as an adjunct in CHD risk assessment. For instance, the finding of an elevated carotid IMT (e.g., >/= 75th percentile for age and sex) could elevate a person with multiple risk factors to a higher risk category. However, its expense, lack of availability, and difficulties with standardization preclude a current recommendation for its use in routine risk assessment for the purpose of modifying intensity of LDL lowering therapy. Even so, if carried out under proper conditions, carotid IMT could be used to identify person at higher risk than that revealed by the major risk factors alone."

However, at the present time there appears to be no scientific literature that directly and experimentally tests the hypothesis that measurement of carotid IMT results in improved patient outcomes, and no specific guidance on how measurements of carotid IMT should be incorporated into risk assessment and risk management.

A literature search performed for the period of 2003 through June 2005 did not identify any published articles that would address the limitations noted above. There continues to be research interest in carotid intimal thickness as a technique to study the pathogenesis of atherosclerosis, and studies continue to include carotid IMT as an intermediate outcome, but its role in the management of the individual patient remains unclear.

2007 Update

The U.S. Preventive Services Task Force does not comment on this testing in their recommendations. Studies continue to report a relationship between subclinical atherosclerosis, as measured by carotid intimal-medial thickness, and incipient myocardial disease (Fernandes et al, 2006). However, the role of this information in improving clinical outcomes has not yet been demonstrated in clinical trials. One recently published report (SHAPE guideline) recommends this testing in many adults (Naghavi et al, 2006). The evidence base for this conclusion is weak (as noted above); in addition, other questions have been raised about the process used in developing this report. Thus, the policy statement is unchanged.

The policy was updated with a literature search using MEDLINE in November 2007. While a number of articles were identified that continue to identify carotid IMT as a risk factor and marker for atherosclerotic disease, the use of these results to change clinical outcomes has not been determined (Lorenz et al, 2007) (Roman et al, 2006) (Manolio et al, 2007). As another potential use, Kanwar reported on the use of carotid IMT in 50 symptomatic patients to improve the ability of stress testing to diagnose clinically significant coronary artery disease (Kanwar et al, 2007). In this study, the carotid IMT did improve patient identification; however, larger trials with a broader spectrum of patients are needed to further evaluate these findings.

2009 Update

A literature search of the MEDLINE database was conducted. No studies were identified that would prompt a change in the coverage policy statement.

The U.S. Preventive Services Task Force published guidelines for the use of emerging risk factors for coronary heart disease (Hefland, 2009). According to the results of the systematic review, the scientific evidence does not support the routine use of carotid intima-media thickness for further risk stratification of persons with intermediate risk for coronary heart disease.

2012 Update

This policy is being updated with a literature search using the MEDLINE database through June 2012. There was no new information identified that would prompt a change in the coverage statement. A summary of the key identified literature follows.

Diagnostic Utility

Systematic reviews. In a 2012 meta-analysis of individual participant data pooled from 16 studies with a total of 36,984 patients, Lorenz and colleagues examined carotid intima-medial thickness (CIMT) progression from 2 ultrasound screenings taken 2-7 years apart (median 4 years) (Lorenz, 2012). Patients were followed for a mean of 7 years during which time 1,339 strokes, 1,519 myocardial infarctions (MI) and 2,028 combined endpoints (MI, stroke, vascular death) occurred. The mean CIMT of the 2 ultrasounds results was predictive of cardiovascular risk using the combined endpoint (adjusted hazard ratio [HR]: 1.16, 95% confidence interval [CI]: 1.10-1.22). In sensitivity analyses, no associations were found between cardiovascular risk and individual CIMT progression regardless of CIMT definition, endpoint, and adjustments. As an example, for the combined endpoints, an increase of one standard deviation (SD) in mean common CIMT progression resulted in an overall estimated HR of 0.97 (95% CI: 0.94-1.00) when adjusted for age, sex, and mean common CIMT, and HR was 0.98 (0.95-1.01) when adjusted for vascular risk factors. These data confirm that CIMT is a predictor of cardiovascular risk, but do not demonstrate that changes in CIMT over time are predictive of future events.

In a 2012 systematic review of subclinical atherosclerosis imaging techniques, Peters et al. reviewed 12 studies on CIMT that examined reclassification of risk (Peters, 2012). For the impact on the primary outcome of cardiovascular events, when CIMT was added to the prediction model, the range of increase in the c-statistic was 0.00 to 0.03 on a scale of 0-1.0. Net reclassification improvement with CIMT was reported in 5 of the studies included in the review and ranged from -1.4% to 12%.

Recent studies have found including carotid plaques in CIMT increases the predictive value of cardiovascular risk over CIMT assessed only in plaque-free sites (Pilchart, 2011) (Keo, 2011) (Nambi, 2012) (Xie, 2011). However, the meta-analysis by Lorenz found no difference in the main results between studies that included CIMT with carotid plaque and plaque-free CIMT (Lorenz, 2012). The systematic review by Peters found adding carotid plaque to the traditional CIMT model increased the c-statistic from 0.01 to 0.06 (Peters, 2012).

In 2010, Mookadam and colleagues conducted a systematic review of the role of CIMT in predicting individual cardiovascular event risk and as a tool in assessing therapeutic interventions (Mookadam, 2010). The authors concluded that CIMT is an independent risk factor for cardiovascular events and may be useful in determining treatment when there is uncertainty regarding the approach or patient reluctance. However, further studies are needed to identify the best approaches to screening and interventions to prevent progression of atherosclerosis.

The Carotid Atherosclerosis Progression Study (CAPS) was a longitudinal study of 4,904 subjects. All subjects received a baseline CIMT measurement, as well as traditional risk factor analysis, and were followed over a 10-year period (mean follow-up 8.5 years, range 7.1-10.0 years). Adverse outcome events were MI in 73 patients (1.5%), angina or MI in 271 patients (5.5%), and death in 72 subjects (1.5%). Lorenz et al. have recently published a retrospective review of the data from CAPS (Lorenz, 2010). The authors modeled the predictive value of CIMT on the cardiovascular adverse events within that decade. Because the thresholds of CIMT measurements that would lead to reclassification of risk are unknown, the authors used 24 different models of reclassification and 5 statistical tests. Each model compares the predictive value of traditional risk factors alone with those risk factors with the addition of CIMT. The authors were unable to find significance in the reclassification models with the addition of CIMT measurements. They concluded that this retrospective analysis does not support the use of CIMT as a clinically useful risk classification tool when used in conjunction with traditional risk factor analysis.

In the Multi-Ethnic Study of Atherosclerosis (MESA) trial, an ongoing cohort study of atherosclerosis, (Folsom, 2008) CIMT was found to be a modestly better predictor of stroke but a worse predictor of CHD than coronary artery calcium score at a median follow-up of 3.9 years among 6,698 adults asymptomatic at baseline. In a 2010 article from MESA, CIMT results in 4,792 healthy, nondiabetic adults who were not on lipid-lowering medications were compared in 6 different lipid groups, including normolipemia and several types of common dyslipidemias (Paramsothy, 2010). The mean CIMT values were increased only for the combined hyperlipidemia (defined as any high-density lipoprotein (HDL)-C level, LDL-cholesterol [C] >160 and triglyceride >150) and simple hypercholesterolemia (defined as any HDL-C level, LDL-C >160 and triglyceride <150) groups. In another MESA report, in 2011, on 6,760 patients with elevated high-sensitivity C-reactive protein (hsCRP) as defined by the JUPITER study, CIMT increases correlated with obesity but only mildly with hsCRP (Blaha, 2011). In the Bogalusa Heart Study of 991 subjects, obesity along with overweight and elevated metabolic risk were also associated with increased CIMT (Camhi, 2011). In this study population, 41% of patients were found to have increased CHD risk. In the CARDIA study, clotting factor VII was associated with increases in CIMT in 1,254 subjects (Green, 2010). CIMT is also used as a surrogate outcome measure in atherosclerosis treatment research studies (Bots, 2009).

In 2010, Raiko et al. compared cardiovascular disease risk-scoring tools for identification of CHD risk to CIMT results in 2,204 healthy adults, aged 24-39 years, from the Cardiovascular Risk in Young Finns study (Raiko, 2010). The cardiovascular disease risk scoring tools evaluated included the Framingham, Reynolds Risk Score, Systematic Coronary Risk Evaluation (SCORE), PROCAM, and Finrisk cardiovascular risk scores. In this population-based follow-up study, the authors found all of the cardiovascular disease risk scores performed equally in being able to predict subclinical atherosclerosis as measured by high CIMT 6 years later.

Conclusions. Evidence from large, prospective cohort studies has established that CIMT is an independent risk factor for cardiovascular disease. However, systematic reviews have concluded that the ability of CIMT to reclassify patients into clinically relevant categories is modest and may not be clinically important. The uncertainty around the ability to reclassify patients into clinically relevant categories limits the potential for CIMT to improve health outcomes.

Clinical Utility

In a 2011 study by Johnson and colleagues, 355 patients, aged 40 years with one or more cardiovascular disease risk factor, received carotid ultrasound screenings to prospectively determine whether abnormal results would change physician and patient behaviors (Johnson, 2011). Results were considered abnormal (when CIMT was greater than the 75th percentile or the presence of carotid plaque) in 266 patients. Self-reported questionnaires were completed before the carotid ultrasound, immediately after the ultrasound, and 30 days later to determine behavioral changes. Physician behavior in prescribing aspirin and cholesterol medication changed significantly (p<0.001 and p<0.001, respectively) after identification of abnormal carotid ultrasound results. Abnormal ultrasound results predicted reduced dietary sodium (odds ratio [OR]: 1.45; P = .002) and increased fiber intake (OR: 1.55; P=0.022) in patients but no other significant changes. Health outcomes were not evaluated in this study, and the short-term follow-up limits interpretation of results.

The evidence on reclassification of cardiovascular risk offers a potential indirect chain of evidence to improve outcomes. If a measure is able to reclassify patients into risk categories that have different treatment approaches, then clinical management changes may occur that lead to improved outcomes. Since the ability to reclassify patients into clinically relevant categories with CIMT is modest at best, the clinical utility of this measure for reclassification is uncertain.

Conclusions. There is no direct evidence on the clinical utility of measuring CIMT for cardiac risk stratification. The available evidence on reclassification into clinically relevant categories does not support that the use of CIMT will improve health outcomes.

Ongoing Trials

A search of the online site ClinicalTrials.gov database in June 2012 identified one open, randomized, controlled trial. The IMPRESS Study (NCT01330602) will randomly stratify 1,310 subjects with an intermediate risk of cardiovascular events and a family history of premature atherosclerosis to either a disease management program with intensive pharmacologic and behavioral interventions for primary prevention or usual health care management. The study will evaluate whether the disease management program is effective and whether changes in CIMT over 3 years can determine atherosclerotic status and future cardiovascular events.

Practice Guidelines and Position Statements

In October 2009, the U.S. Preventive Services Task Force (USPSTF) published a systematic review of CIMT within the scope of a larger recommendation statement entitled “Using Nontraditional Risk Factors in Coronary Heart Disease Risk Assessment” (USPSTF, 2009). On the basis of one fair- and 2 good-quality studies, the USPSTF states that CIMT, independently of Framingham risk factors, predicts coronary heart disease (CHD) in asymptomatic patients. These studies were longitudinal, population-based studies conducted in the U.S. and the Netherlands. USPSTF reviewed the Atherosclerosis Risk in Communities (ARIC) study and concluded that CIMT measurement can result in risk prediction that is modestly improved, particularly in adult men. However, the review cautions that the studies that did show an association were all done in a research setting, and therefore one cannot draw conclusions on the applicability of CIMT to the intermediate-risk population at large.

The Summary of Recommendation specific to CIMT is stated as: “The U.S. Preventive Services Task Force (USPSTF) concludes that the current evidence is insufficient to assess the balance of benefits and harms of using…[CIMT]…to screen asymptomatic men and women with no history of CHD to prevent CHD events.” The USPSTF identifies the following research need: “The predictive value…of carotid IMT…should be examined in conjunction with traditional Framingham risk factors for predicting CHD events and death.”

The 2010 American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines (Greenland, 2010) indicate: “Measurement of carotid artery IMT is reasonable for cardiovascular risk assessment in asymptomatic adults at intermediate risk.” The guidelines note an increased CIMT reading may be used as a guide in determining clinical treatment, but evidence has not demonstrated improvements in outcomes when incorporating CIMT measurement into treatment decision making. Additionally, the Guidelines state: “Clinical tools integrating carotid IMT within global risk scoring systems are not available. The incremental value of carotid IMT and cost effectiveness beyond that available from standard risk assessments to improve overall patient outcomes is not established.” Furthermore, “serial scanning of carotid IMT is challenging in individual patients across brief time horizons due to variability in measurement in relation to the rate of disease progression and is therefore not recommended in clinical settings.”

Summary

Ultrasonographic measurement of carotid intima-medial (or intimal-media) thickness (CIMT) refers to the use of B-mode ultrasound to determine the thickness of the 2 innermost layers of the carotid artery wall, the intima and the media. Detection and monitoring of intima-medial thickening, which is a surrogate marker for atherosclerosis, may provide an opportunity to intervene earlier in atherogenic disease and/or monitor disease progression.

Some studies correlate increased CIMT with many other commonly used markers for risk of CHD and with risk for future cardiovascular events. While a 2012 meta-analysis of individual participant data by Lorenz et al. found that CIMT was associated with increased cardiovascular events, CIMT progression over time was not associated with increased cardiovascular event risk. In a systematic review by Peters and colleagues, (Peters, 2012) the added predictive value of CIMT was modest, and the ability to reclassify patients into clinically relevant categories was not demonstrated. The results from these studies and others demonstrate the predictive value of CIMT is uncertain, and the predictive ability for any level of population risk cannot be determined with precision.

In addition, available studies do not define how the use of CIMT in clinical practice improves outcomes. There appears to be no scientific literature that directly and experimentally tests the hypothesis that measurement of CIMT results in improved patient outcomes and no specific guidance on how measurements of CIMT should be incorporated into risk assessment and risk management. The existing data are insufficient to determine the impact of this technology on net health outcome.

2014 Update

A literature search conducted using the MEDLINE database through July 2014 did not reveal any new information to prompt a change in the coverage statement.

A 2013 guideline on the assessment of cardiovascular risk from the American College of Cardiology and the American Heart Association (ACC/AHA) does not recommend CIMT for routine risk assessment of a first atherosclerotic cardiovascular disease event. (Grade N, not recommendation for or against) ACC/AHA Class III: no benefit, LOE: B. (based on new evidence during ACC/AHA update of evidence) (Goff, 2013). This differs from the previous 2010 version of the ACC/AHA guidelines for assessment of cardiovascular risk,(Greenland, 2010) which indicated CIMT might be reasonable for assessing cardiovascular risk in intermediate risk asymptomatic adults.

2015 Update

A literature search using the MEDLINE database conducted through July 2015 did not identify any new information that would prompt a change in the coverage statement.

The BioImage study enrolled 5808 asymptomatic individuals from the United States (Baber, 2015). All patients were evaluated by 3-dimensional carotid ultrasound and by coronary artery calcification score, and followed for a mean of 2.7 years. The primary endpoint was major cardiovascular events, defined as cardiovascular death, MI, and ischemic stroke. The carotid plaque burden was an independent predictor of outcomes, with a hazard ratio of 2.36 (95% CI, 1.13 to 4.92) for individuals in the highest tertile. The coronary calcium score was also an independent predictor of outcomes, with similar hazard ratios to carotid plaque. Both carotid plaque and coronary calcium score led to significant net reclassification, with a net reclassification index of 0.23.

2017 Update

A literature search conducted through June 2017 did not reveal any new information that would prompt a change in the coverage statement. The key identified literature is summarized below.

A 2015 report from MESA trial of 6125 individuals with a family history of premature CHD identified 382 atherosclerotic CAD events at a mean follow-up of 10.2 years (Patel, 2015). The study found that CAC improved the risk estimation atherosclerotic CAD events but CIMT did not.

ONGOING AND UNPUBLISHED CLINICAL

Some currently unpublished trials that might influence listed below:

Ongoing

(NCT01849575) Direct VIsualiZAtion of Asymptomatic Atherosclerotic Disease for Optimum Cardiovascular Prevention. A Population Based Pragmatic Randomised Controlled Trial Within Västerbotten Intervention Programme (VIP) and Ordinary Care; planned enrollment 3200; projected completion date June 2021

2018 Update

A literature search was conducted through July 2018. There was no new information identified that would prompt a change in the coverage statement. The key identified literature is summarized below.

ULTRASONOGRAPHIC MEASUREMENT OF CIMT

Prospective Cohort Studies

Geisel et al conducted a prospective cohort study of 3108 patients without CVD on entrance to the study (Geisel, 2017). All patients were evaluated for traditional risk factors of CVD; they were also assessed to calculate the CIMT, CAC score, and Ankle-Brachial Index score. During a mean follow-up of 10 years, 223 individuals suffered a major cardiovascular event (coronary event, stroke, CV death). All 3 methods helped predict adverse cardiovascular events. While CIMT was found to be higher in those who experienced an adverse cardiovascular event (0.76) than those who did not (0.69), CIMT did not significantly improve the prediction of cardiac risk for patients with an intermediate Framingham Risk Score.

Villines et al prospectively assessed a cohort of 3801 African American patients free of CVD at baseline (Villines, 2017). Over a median follow-up of 9 years, there were 171 new cases of CVD and 339 deaths. The incidence of cardiovascular events correlated with changes in CIMT and participants in the highest CIMT quartile had the largest unadjusted incident rates of CVD for both men and women. However, risk reclassification improved only slightly when adding CIMT to a model that included only traditional risk factors for CVD.

PRACTICE GUIDELINES AND POSITION STATEMENTS

American Association of Clinical Endocrinologists et al

The American Association of Clinical Endocrinologists and American College of Endocrinology published guidelines stating that CIMT could be applied as a risk stratification tool in determining the need for more aggressive preventive strategies against cardiovascular disease (grade B; best evidence level 2) but not routinely (AACE, 2017).

2019 Update

Annual policy review completed with a literature search using the MEDLINE database through July 2019. No new literature was identified that would prompt a change in the coverage statement.

2020 Update

Annual policy review completed with a literature search using the MEDLINE database through July 2020. No new literature was identified that would prompt a change in the coverage statement. The key identified literature is summarized below.

In 2008, the American Society of Echocardiography consensus statement, endorsed by the Society for Vascular Medicine, stated that CIMT is a feature of arterial wall aging "that is not synonymous with atherosclerosis, particularly in the absence of plaque (Stein, 2008)." The statement recommended measurement of both CIMT and carotid plaque by ultrasound "for refining CVD [cardiovascular disease] risk assessment in patients at intermediate cardiovascular disease risk (Framingham Risk Score 6%-20%) without established CHD [coronary heart disease], peripheral arterial disease, cerebrovascular disease, diabetes mellitus, or abdominal aortic aneurysm." However, Society acknowledged that "More research is needed to determine whether improved risk prediction observed with CIMT or carotid plaque imaging translates into improved patient outcomes."

In 2009, the U.S. Prevention Services Task Force (USPSTF) published a systematic review of CIMT within the scope of a larger recommendation on the use of nontraditional risk factors in coronary heart disease risk assessment (Calonge, 2009).,The USPSTF could not draw conclusions on the applicability of CIMT to the intermediate-risk population at large outside the research setting. The USPSTF summary of recommendation specific to CIMT stated that: “… the current evidence is insufficient to assess the balance of benefits and harms of using … [CIMT] … to screen asymptomatic men and women with no history of CHD to prevent CHD events.” The USPSTF identified the following research need: “The predictive value … of carotid IMT … should be examined in conjunction with traditional Framingham risk factors for predicting CHD events and death.”

In 2018, the USPSTF published a recommendation statement on using nontraditional risk factors to assess risk of cardiovascular disease; CIMT was not mentioned in this recommendation (Curry, 2018).

2021 Update

Annual policy review completed with a literature search using the MEDLINE database through July 2021. No new literature was identified that would prompt a change in the coverage statement. The key identified literature is summarized below.

Bytyçi et al published a meta-analysis of 89 studies and found that CIMT was significantly higher in patients with CAD versus controls (p<.001) (Bytyci, 2021). A moderate correlation was found between CIMT and severity of CAD (r = 0.60; 95% CI, 0.47 to 0.70; p<.001) and the number of diseased vessels (r = 0.49; 95% CI, 0.36 to 0.59; p<.001). CIMT ≥ 1.0 mm had a summary sensitivity of 77% (range, 70% to 85%), summary specificity of 72% (range, 59% to 82%), positive predictive value of 82% (range, 80% to 83%), negative predictive value of 66% (range, 64% to 68%), and an accuracy of 76% (range, 74% to 77%) for predicting significant CAD.

Tschiderer et al published a meta-analysis of 7 prospective studies examining the extent to which CIMT predicts the incidence of carotid plaque in individuals free of carotid plaque at baseline (Tschiderer, 2020). Results showed that when individuals in the top fourth of baseline CIMT distribution were compared with those in the bottom fourth, the relative risk for incidence of first-ever carotid plaque was 1.78 (95% CI, 1.53 to 2.07; p<.001).

The recommendations made in the 2008 American Society of Echocardiography consensus statement were endorsed in ASE's 2020 guideline entitled Recommendations for the Assessment of Carotid Arterial Plaque by Ultrasound for the Characterization of Atherosclerosis and Evaluation of Cardiovascular Risk (Johri, 2020). Authors of the 2020 guideline also note the following: "Since the largest portion of CIMT (approximately 99% in healthy individuals and approximately 80% when diseased) consists of the medial layer, CIMT has not been shown to consistently add to CVD risk prediction."

2022 Update

Annual policy review completed with a literature search using the MEDLINE database through July 2022. No new literature was identified that would prompt a change in the coverage statement.

2023 Update

Annual policy review completed with a literature search using the MEDLINE database through July 2023. No new literature was identified that would prompt a change in the coverage statement.

CPT/HCPCS:

References:

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Baber U, Mehran R, Sartori S, et al.(2015) Prevalence, impact, and predictive value of detecting subclinical coronary and carotid atherosclerosis in asymptomatic adults: the BioImage study. . J Am Coll Cardiol. Mar 24 2015;65(11):1065-1074. PMID 25790876

Blaha MJ, Rivera JJ, Budoff MJ et al.(2011) Association between obesity, high-sensitivity C-reactive protein =2 mg/L, and subclinical atherosclerosis: implications of JUPITER from the Multi-Ethnic Study of Atherosclerosis. Arterioscler Thromb Vasc Biol 2011; 31(6):1430-8.

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